Dextran benzyl phthalate



Patented Jan. 28, 1941 DEXTRAN BENZYL PHTHALATE Grant L. Stahly and Warner W. Carlson, Columbus, Ohio, assignors to Commonwealth Engineering Corporation, Wilmington, Del., a corporation of Delaware No Drawing.

Original application November 4,

1938, Serial No. 238,855. Divided and this application August 21,

6 Claims.

This invention relates to the production of polysaccharide materials by the action or various micro-organisms on suitable culture media, and to processes for converting these polysaccharides t into their ether, mixed ether, ester, mixed ester or mixed ether-ester derivatives.

It is the object of this invention to produce polysaccharide materials by the action of various micro-organisms on suitable culture media and W in particular to produce dextran; and to thereafter subject the polysaccharide materials such as dextran to a process of etherification or esterihcation either while the materials are in the culture media or after separation therefrom so I as to produce the new products of resinous character such as the benzyl ether of dextran, the butyl ether of dextran, etc.

The polysaccharides are produced by inoculatlrfg media containing sucrose, nitrogenous compounds and various salts with bacteria of known genus and species. These bacteria may be placed in one of two groupings, those that produce polysaccharides known as levans, or those that produce the polysaccharides known as dextrans.

25 The two types of polysaccharides are distinguished from one another by the fact that on hydrolysis with acids or enzymes, the dextrans yield only dextrose while the levans yield only levulose. As specific examples, Bacillus meson- 30 terious, B. subtilis, B. megatherium, Pseudomonas pruni, Ps. prunicola or Ps. phaseoli may be employed for the production of the levan type of polysaccharide, while Leuconostoc mesenterioldes or L. dextranicum may be used for the production 35 or the dextran type.

The culture media employed should preferably contain some sucrose; this can be either refined or crude sucrose, molasses or any similar sucrose containing material. Nitrogen may be added in 40 the form of commercial peptone, beef extract or other nitrogen containing material. If molasses is used as the sucrose source, nitrogenous com pounds in suflicient quantity are present in it so that none need be added. Salts such as dipotas- 45 slum phosphate and sodium chloride are also added. As a specific example, a typical medium may contain: sucrose, 5-10%, peptone, 0.1%, dipotassium phosphate 0.2% and sodium chloride 0.1%. The pH of the medium preferably is ad- 50 iusted to slightly on the alkaline side of neutrality. 1

The production of the polysaccharide is favored by keeping the reaction of the media slightly alkaline throughout the'period of fer- 5 mentation. This may be accomplished by the 1939, Serial No. 291,189

periodic addition of alkali to the fermenting media or by using an excess ofcalcium carbonate in the media. After inocculation the cultures are incubated at the temperature most favorable to the growth of the micro-organism being used. For one of the preferred forms, Leuconostoc mesenterioides, this temperature is around 25 degrees C. The progress of the fermentation may be followed by periodically removing samples of the fermenting culture media and precipitating the polysaccharide contained in them by the addition of three to five times their volume of alcohol. The precipitated polysaccharide may then be weighed. When a maximum oi polysaccharide has been formed the culture media are ready for the etherification or esterificatlon processes. The length of time necessary for the maximum of polysaccharide to be formed will vary with the organism employed, the temperature of incubation, the concentration of sucrose and other factors.

The polysaccharlde may be isolated from the solution by precipitation with alcohol or acetone. Preferably the reaction of the fermented medium is first adjusted to the neutral point to lessen the possibility of hydrolysis of the polysaccharide, and the solution then concentrated under reduced pressure at a temperature of 40 to 50 degrees C. to approximately one-fourth its original volume. The solution is then poured, with stirring, into three to five times its volume of alcohol or acetone. The polysaccharide may be precipitated directly from the fermented culture media by the addition of alcohol or acetone, but it is then necessary to use a considerably larger amount of the precipitating agent.

For the preparation of the ether and ester derivatives of these polysaccharides it is not necessary that they first be isolated from the culture media in which they were formed. In- 1 stead the necessary reagents may be added directly to the fermented media, and after completion of the reaction, the ether, ester, or mixed ether-ester derivatives can be recovered from the mixture, either by a simple mechanical process in case the product is water insoluble, or by the use of specific precipitating agents.

If, however, the polysaccharide is not removed from the culture solution before esterification or etheriflcation, the product obtained is a mixture of compounds. It will contain, besides the ethers and/or esters of the polysaccharide, the corresponding derivatives of any excess sucrose or metabolic products remaining in the fermented culture media. In some cases this may be desirable since a blending of these various derivatives yields a product with a range of solubilities. However, in cases in which a product with the specific properties of the polysaccharide derivative alone is desired, it is necessary either to separate the dextrans or levans from the culture media before chemical treatment, or else to remove the undesirable by-products, from the mixture obtained by the direct treatment 01 the fermented media, by the use of specific solvents.

Whether the fermented media are treated directly, or the polysaccharides first isolated by alcohol or acetone precipitation, the proportions of the reactants used in the preparation of the ether derivatives are approximately as follows: one moi of the polysaccharide, 3.5 mols of the alkyl or aralkyl halide and 4.5 mols of sodium hydroxide. If the polysaccharide was isolated from the medium before the chemical treatment, suflicient water must be added to the mixture so as to yield approximately a 10 per cent solution of the sodium hydroxide.

If the fermented culture medium itself is used, the amount of water present should be so regulated by concentration or dilution to again yield approximately a 10 per cent solution of the alkali. After addition of the reagents the mixture is heated for a predetermined time, usually 4 to 6 hours, at a temperature anywhere from to 130 degrees C. This temperature depends on the derivative being prepared.

In general, the higher the temperature and the longer the period of heating the greater will be the number of hydroxyl groups in the polysaccharide which will be substituted by the organic radical of the halide compound used. The temperature and time of heating employed is consequently governed by the type of product desired. The organic halide used may be any member of the aliphatic series such as methyl chloride, ethyl chloride, propyl or isopropyl chloride,

'butyl chloride or any of its isomers, etc., or any one of the aralkyl series such as benzyl chloride.

The aliphatic derivatives are water soluble, at least as high as the butyl derivative, but we do not know whether insoluble derivatives can be produced if the reaction is carried out in a pressure vessel. The benzyl ethers are generally water insoluble. Regardless of the type of organic halide used, increasing the proportion of halide to polysaccharide, running the reaction at a higher temperature and for a longer period of time will generally result in a decreased water solubility for the products obtained.

It is to be understood that the organic halide used may be either the chloride, bromide or iodide derivative. For purposes of economy, the chlorides are generally employed.

At the conclusion of the reaction period excess halide is recovered by any suitable process such as steam distillation. The product is isolated by mechanical means if it is water insoluble or by precipitation if it is water soluble.

The process may be varied by the simultaneous introduction of two or more organic halide compounds into the reaction mixture, in which case the product will be a mixed ether; or a particular ether derivative may be prepared and the product from the reaction then treated with a difierent organic halide to yield a mixed ether derivative. Again, an ether derivative may be prepared and then further treated with organic acid chlorides, acid anhydrides or the like for the preparation of mixed ether-esterv derivatives. Such variations products. It will be understood we do not desire to be confined to the detailed proportions, temperatures and pressures, although we are reciting hereinafter those that we have found to be the preferred temperatures and other conditions.

It will be further understood that it is comprehended within this process the production of a large number of allied materials.

It will be further understood that we are illustrating the process and the materials that can be produced by typical materials within which we comprehend other similar new materials.

EXAMPLE I Benzyl ether derivatives This process may be carried out directly on the fermented culture media containing the polysaccharide, such as dextran, although the same process can be employed with the extracted dextran after it has been removed from the culture media. This statement applies to the other I examples hereinafter recited.

To a portion of the fermented culture medium in which the polysaccharide has been produced and in which there is approximately 30 gm. of the polysaccharide, is added gm. of benzyl chloride and 40 gm. of sodium hydroxide. The resulting mixture is heated for approximately five hours. If the temperature is held at 80 to 85 degrees C., the crude product is light orange in color and soft and rubbery in consistency. When higher temperatures of from to degrees C. are employed, an orange-brown product is obtained 01' the same consistency but of greater resistance to solvents. The time of heating may range from 4 to 6 hours but 5 hours is the preferable time. By varying the temperature of this benzylation process, the solubilities in various solvents of the resulting products are varied. These products are substantially insoluble in water.

EXAMPLE II Butyl ether derivatives To a portion of the fermented culture medium containing 30 gm. of dextran, we add gm. of butyl chloride and 40 gm. of sodium hydroxide. The mixture is heated at 100 degrees C. for four hours. The derivative is an amorphous mass that is water soluble.

Exmu. III

Mixed benzyl ether-butul ether derivatives To a water solution of the butyl ether derivative is added benzyl chloride and sodium hydroxide in the proportion of 30 gm. of the butyl ether; 90 gm. of benzyl chloride and 40 gm. of sodium hydroxide. The mixture is heated at 80 to 85 degrees C. for a period of five hours. After removal of excess benzyl chloride and benzyl alcohol by steam distillation, the resulting product is isolated as a rather firm and leathery amorphous mass.

EXAMPLE IV Beta-hydroxy ethyl ether derivatives.

siderable amount of gas was given oil and thecolor changed to a light brown. Since the betahydroxy ethyl ether derivative is water soluble it was isolated by precipitation with acetone. The product was an amorphous, hygroscopic mass.

EXAMPLEV Mixed beta-hydroxy ethyl ether-benzyl ether derivatives.

To a water solution of the beta-hydroxy ethyl ether derivative was added benzyl chloride and 7 sodium hydroxide in the proportion 30 gm. of the ether, 90 gm. of benzyl chloride and 40 gm. of alkalif The mixture was heated at to degrees C. for five hours. After removal of excess benzyl chloride and benzyl alcohol by steam distillation, the resulting product appeared as a golden-brown, rather moist and stringy amorphous mass.

EXAMPLE VI M ixed butyl ether-benzoyl ester derivative To 20 gm. of the butyl ether derivative of dex- Mixed benzyl ether-phthalyl ester derivative To a dioxane solution of the benzyl ether derivative was added an alcoholic solution 01' anhydrous zinc chloride and phthalic anhydride in the proportions, 10 gm. of the benzyl ether, 4 gm. of anhydrous zinc chloride, and 10 gm. of phthalic anhydride. The mixture was refluxed at to degrees C. for ten hours. The resulting product as precipitated by acetone was a semi-transparent, horny amorphous mass.

It will be understood that the temperatures and times are relative and may be varied within reasonable limits to secure the objectives desired.

The dextran derivative products produced by the method 01 this invention are adapted for use as a film forming constituent in formulating coating compositions and may be utilized in the manufacture of plastics, molded products, synthetic rubber and the like articles of manuiacture.

This application is a division of our application Serial No, 238,855, filed November 4, 1938.

It will be understood thatwe desire to comprehend within this invention such modifications as come within the scope of our claims and our invention.

Having thus fully described our invention, what we claim as new and desire to secure by Letters Patent is:

1. In a method of making ester derivatives of bacteriologically formed dextran, forming the benzyl ether derivative of dextran by reacting the dextran with benzyl chloride in the presence of sodium hydroxide, adding dioxane to form a solution of the benzyl ether derivative, and mixing therewith an alcoholic solution of anhydrous zinc chloride and phthalic anhydride, reacting the mixture together to produce the mixed benzyl ether-ester derivative of dextran.

2. In a method of making ester derivatives of dextran bacteriologically produced from sucrose, reacting the dextran with benzyl chloride and sodium hydroxide to produce a benzyl ether derivative thereof, forming a. dioxane solution of the benzyl ether derivative, adding thereto an alcoholic solution of anhydrous chloride and phthalic anhydride, reacting the mixture together with the application of heat for several hours, and precipitating the product produced comprising the amorphous ester derivative of dextran.

3. A method of making mixed esters of dextran, comprising inoculating a culture medium containing sucrose with bacteria of the Leuconostoc species to produce dextran, reacting the mixture with sodium hydroxide solution of an organic aralkyl halide to produce an ether derivative of dextran, reacting said ether derivative with an alcoholic solution of anhydrous metal halide and phthalic anhydride to form a mixed ester derivative of dextran, and separating out the dextran ester product formed.

4. A method of making a mixed benzyl etherester derivative of dextran, comprising forming a dioxane solution oi! benzyl ether of dextran, adding an alcoholic solution of anhydrous zinc chloride and phthalic anhydride, heating the mixture to form a reaction product, and precipitating the product from the solution by the addition of acetone.

5 A method of making mixed ether-ester derivatives of dextran, comprising forming a dioxane solution of benzyl ether of dextran. adding thereto an alcoholic solution 0! anhydrous zinc chloride and phthalic anhydride, refluxing the ingredients at a temperature of approximately 100 degrees C. for several hours, and recovering the benzyl ether-ester of dextran formed.

6. A method or making a benzyl ether-ester derivative of dextran, comprising forming a solution of benzyl ether of dextran in dioxane. adding an alcoholic solution of anhydrous zinc chloride and phthalic anhydride in the proportion by weight of 10 parts of benzyl ether of dextran, 4 parts of anhydrous zinc chloride and 10 parts of phthalic anhydride. refluxing the solution at 95 degrees to 100 degrees C. for 10 hours, and recovering the benzyl ether-ester derivative of dextran.

GRANT L. STAHLY. WARNER W. CARLSON. 

